The long term objective of this proposal is to understand central nervous system (CNS) mechanisms involved in the modulation of nociceptive (painful) sensory input. This knowledge will provide a better understanding of the mechanisms involved in the actions of drugs which interact with these systems, such as opioid analgesics. The rostral ventromedial medulla (RVM) is an area in the CNS that modulates spinal nociceptive sensory input via descending neuronal projections and contains the neuropeptide neurotensin. The goal of this proposal is to determine the effects of neurotensin in the RVM on spinal dorsal horn neuronal responses to a variety of noxious stimuli. Extracellular recording of isolated spinal units responding to noxious cutaneous thermal, mechanical, and visceral stimuli will be performed in anesthetized rats. Dose-dependent effects of neurotensin microinjected into the RVM on these responses will be characterized. Neurotensin receptor mediated effects and potential receptor subtypes will be determined using specific neurotensin receptor antagonists. Finally, descending spinal tracts mediating neurotensin effects from the RVM will be determined by selectively inactivating the dorsolateral or ventrolateral funiculi.